Sprouting of substance P-expressing primary afferent central terminals and spinal micturition reflex NK1 receptor dependence after spinal cord injury.
The primary afferent neurotransmitter triggering the spinal micturition reflex after complete spinal cord injury (SCI) in the rat is unknown. Substance P detected immunohistochemically in the sacral parasympathetic nucleus was significantly higher in 12 SCI rats than in 12 spinally intact rats (P = 0.008), suggesting substance P as a plausible candidate for the primary afferent neurotransmitter. The effects of the tachykinin NK1 receptor antagonist L-733060 on the spinal micturition reflex were then determined by performing conscious cystometry in an additional 14 intact rats and 14 SCI rats with L-733060 (0.1-100 microg) administered intrathecally at L6-S1. L-733060 was without effect in intact rats, but blocked the spinal micturition reflex in 10 of 14 SCI rats and increased the intermicturition interval in 2 of 4 others at doses ranging from 10 to 100 microg. Both phasic and nonphasic voiding contractions, differentiated according to the presence of phasic external urethral sphincter (EUS) activity, were present in most SCI rats. Both types of contractions were blocked by high doses of L-733060. Interestingly, there was a relative decline in phasic voiding contractions at high doses as well as a decline in contraction amplitude in nonphasic voiding contractions. In other respects, cystometric variables were largely unaffected in either spinally intact or SCI rats. L-733060 did not affect tonic EUS activity at any dose except when the spinal micturition reflex was blocked and tonic activity was consequently lost. These experiments show that tachykinin action at spinal NK1 receptors plays a major role in the spinal micturition reflex in SCI rats.
Zhang
Xiaoyang
X
Department of Surgery, Veterans Affairs Medical Center, Duke University Medical Center, Durham, NC 27710, USA.
Douglas
Kristy L
KL
Jin
Huixia
H
Eldaif
Bassem M
BM
Nassar
Rashid
R
Fraser
Matthew O
MO
Dolber
Paul C
PC
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005260:Female; D007278:Injections, Spinal; D009119:Muscle Contraction; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D010880:Piperidines / Q000008:administration & dosage; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects; D020760:Spinal Cord Ischemia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013127:Spinal Nerves / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013373:Substance P / Q000378:metabolism*; D013997:Time Factors; D001743:Urinary Bladder / Q000294:innervation* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects
D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C103788:3-((3,5-bis(trifluoromethyl)phenyl)methyloxy)-2-phenylpiperidine; D013373:Substance P